A magnetic nano bimetallic catalyst and its preparation method and catalytic application

Abstract

The present invention relates to the technical field of the synthesis of benzoxazepine compounds, and specifically discloses a magnetic nano bimetallic catalyst, a preparation method thereof, and a catalytic application. In the present invention, NiFe2O4@SiO2 core-shell nanoparticles are selected as the carrier, and the alkoxy groups in the cerium imine ligand are condensed with the hydroxyl groups on the surface of the carrier to form silicon-oxygen bonds, realizing the grafting of the cerium imine ligand on the surface of the magnetic nanoparticles. Subsequently, the O atom in the cerium imine ligand and the N atom in the imine bond coordinate with the transition metal to form a stable six-membered ring structure, successfully anchoring Ce(III) and the transition metal onto the magnetic core-shell nanoparticles to form a bimetallic magnetic nano catalyst. The bimetallic magnetic catalyst provided by the present invention has high catalytic activity, is particularly suitable for catalyzing the synthesis of 1,5-benzoxazepine compounds, is a novel catalyst with great application value, and the catalyst is easy to be magnetically separated and recycled, with broad potential application fields.

Description

Technical Field

[0001] The invention relates to the technical field of synthesis of 1,5-benzoxazepine compounds, and in particular to a magnetic nano bimetallic catalyst and a preparation method and catalytic application thereof. Background Art

[0002] 1,5-Benzodiazepine compounds are an important privileged skeleton composed of a benzene ring and a seven-membered nitrogen-containing heteroatom ring. They have rich pharmacological activities and are effective in treating epilepsy, depression, insomnia, inflammation and other diseases. For example, olanzapine, clozapine, clobazam and nevirapine are already 1,5-benzodiazepine drugs. Therefore, the research on the synthesis method of 1,5-benzodiazepine / nitrogen oxide compounds has attracted extensive attention from medicinal chemists and organic chemists.

[0003] However, unlike 1,5-benzodiazepine compounds, there are few reports on the synthesis of 1,5-benzoxazepine compounds because the organic synthesis reaction of 1,5-benzoxazepine compounds is difficult to carry out. Most of the reported synthetic routes are also achieved through the condensation reaction of carboxylic acid derivatives and aromatic ring halides under strong alkaline catalysis. Most of these reactions have low reaction activity and poor selectivity. There are also disadvantages such as difficulty in recycling catalysts, large amounts of organic waste liquid, and poor environmental protection. At present, a relatively novel synthetic route is to use o-aminophenol and 1,3-dicarbonyl compounds or aldehyde compounds as raw materials, and through nucleophilic addition-elimination, nucleophilic addition, protonation of carbonyl groups, intramolecular CC coupling and other processes to form a benzo-seven-membered oxygen nitrogen heterocyclic structure. This method is greener and more environmentally friendly, but because the hydroxyl group in the substrate o-aminophenol is not as active as the amino group, the reaction requires a catalyst with higher selectivity and catalyticity. Summary of the invention

[0004] In view of the problems of low catalytic activity, poor selectivity and poor reusability of existing catalysts for synthesizing 1,5-benzoxazepine compounds, the present invention provides a magnetic nano bimetallic catalyst and its preparation method and catalytic application. The present invention loads Ce(III) and Cu(II) or Pd(II) bimetallic catalytic active components onto a core-shell structured nickel ferrite magnetic carrier to obtain a stable and efficient bimetallic nanocatalyst, which can be used as a Lewis acid to activate the carbonyl group in the substrate of the nucleophilic substitution reaction, and can also promote the CC coupling reaction in the intermediate molecule, thereby efficiently catalyzing the synthesis reaction of 1,5-benzoxazepine compounds, and the catalyst can be reused multiple times without a significant decrease in catalytic activity.

[0005] In order to solve the above technical problems, the technical solution provided by the present invention is:

[0006] The first aspect of the present application provides a magnetic nano bimetallic catalyst, comprising a NiFe2O4@SiO2 core-shell nanoparticle carrier, and a cerium-based imine ligand and a transition metal Lewis acid chemically bonded and loaded on the carrier;

[0007] Wherein, the structure of the cerium-based imine ligand is shown in formula (X):

[0008]

[0009] Wherein, m=3, 4; R is methyl or ethyl;

[0010] The alkoxy group in the cerium-based imine ligand condenses with the hydroxyl group on the surface of the carrier to form a silicon-oxygen bond; and the N of the imine bond in the cerium-based imine ligand and the O connected to Ce are respectively coordinated with the metal atom in the transition metal Lewis acid to form a six-membered ring.

[0011] Compared with the prior art, the present invention selects NiFe2O4@SiO2 core-shell nanoparticles as carriers, and realizes the grafting of the cerium-based imine ligands on the surface of magnetic nanoparticles by condensing the hydroxyl groups on the surface of the carriers with the alkoxy groups in the cerium-based imine ligands to form silicon-oxygen bonds. After that, the O atoms in the cerium-based imine ligands and the N atoms in the imine bonds coordinate with the transition metals to form a stable six-membered ring structure, successfully anchoring Ce(III) and the transition metals to the magnetic core-shell nanoparticles to form a bimetallic magnetic nanocatalyst. The bimetallic magnetic catalyst provided by the present invention has high catalytic activity, can synergistically catalyze multiple reactions in organic synthesis, is conducive to catalyzing domino reactions to synthesize target products, and is particularly suitable for catalyzing the synthesis of 1,5-benzoxazepine compounds. It is a new catalyst with great application value, and the catalyst is easy to be magnetically separated and recovered, has good chemical stability in the reaction system, and has no obvious decrease in catalytic activity after multiple recycling, and has a wide potential application field.

[0012] Preferably, the transition metal Lewis acid is copper chloride, copper acetate, palladium chloride or palladium acetate.

[0013] Further preferably, the transition metal Lewis acid is copper acetate.

[0014] The preferred transition metal Lewis acid has a higher coordination ability and can form a stronger coordination bond with N and O in the cerium-based imine ligand, thereby forming a stable six-membered ring structure, improving the stability of the transition metal on the carrier surface, thereby improving the stability of the catalyst; in addition, Cu and Pd, especially Cu, have excellent catalytic activity for the synthesis reaction of 1,5-benzoxazepine compounds, and can improve the yield and purity of the target product.

[0015] Preferably, the structure of the magnetic nano bimetallic catalyst is as shown in formula (I):

[0016]

[0017] Wherein, m=3, 4; R is methyl or ethyl; M is CuCl2, Cu(OAc)2, PdCl2 or Pd(OAc)2.

[0018] Further preferably, the structure of the magnetic nano bimetallic catalyst is as follows:

[0019]

[0020] The second aspect of the present application provides a method for preparing the above-mentioned magnetic nano bimetallic catalyst, comprising the following steps:

[0021] Step a, preparing NiFe2O4@SiO2 core-shell nanoparticles;

[0022] Step b, adding cerium acetylacetonate to a first organic solvent, adding an aminosilane coupling agent, mixing evenly, reacting, then adding the NiFe2O4@SiO2 core-shell nanoparticles thereto, heating the reaction, separating the product, washing, and drying to obtain NiFe2O4@SiO2 core-shell nanoparticles loaded with Ce;

[0023] Step c, dispersing the Ce-loaded NiFe2O4@SiO2 core-shell nanoparticles and the transition metal Lewis acid in a second organic solvent, heating for reaction, separating the product, washing, and drying to obtain the magnetic nano bimetallic catalyst. The reaction equation is as follows:

[0024]

[0025] Wherein, m=3, 4; R is methyl or ethyl; M is CuCl2, Cu(OAc)2, PdCl2 or Pd(OAc)2.

[0026] Compared with the prior art, the present invention is based on NiFe2O4@SiO2 core-shell nanoparticles, firstly uses an aminosilane coupling agent to react with cerium acetylacetonate for nucleophilic addition and dehydration to condense to form a cerium-based imine ligand containing an imine bond, and then further condenses the alkoxy group of the silane coupling agent with the hydroxyl group on the surface of the NiFe2O4@SiO2 core-shell nanoparticles to form a silicon-oxygen bond, and then the cerium-based imine ligand is grafted onto the NiFe2O4@SiO2 core-shell nanoparticles, and then the O atoms and N atoms in the cerium-based imine ligand are coordinated with the transition metal to form a stable six-membered ring structure, thereby preparing a series of structurally stable magnetic nano bimetallic catalysts.

[0027] The preparation method of the magnetic nano bimetallic catalyst provided by the present invention has readily available raw materials and green and environmentally friendly reaction conditions. The prepared catalyst has many active centers on the surface and high catalytic activity. The biactive components are firmly anchored on the carrier surface in the form of chemical bonding and six-membered ring coordination, and the chemical stability is good. At the same time, the catalyst also has good magnetic recyclability and efficient cyclic catalytic ability, which is of great significance for the catalytic synthesis of 1,5-benzoxazepine compounds.

[0028] Preferably, in step b, the mass ratio of the NiFe2O4@SiO2 core-shell nanoparticles to cerium acetylacetonate is 1:1.2-1:1.5.

[0029] Preferably, in step b, the mass ratio of the NiFe2O4@SiO2 core-shell nanoparticles to the aminosilane coupling agent is 1:0.6-1:1.

[0030] Preferably, in step b, the first organic solvent is toluene or n-hexane.

[0031] Optionally, in step b, the mass-to-volume ratio of the cerium acetylacetonate to the first organic solvent is 1:20-1:25, wherein the unit of mass is gram and the unit of volume is milliliter.

[0032] Preferably, in step b, the aminosilane coupling agent is 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane or 4-aminobutyltriethoxysilane.

[0033] Preferably, in step b, the reaction temperature of cerium acetylacetonate and aminosilane coupling agent is 10° C.-30° C., and the reaction time is 12 h-13 h.

[0034] Preferably, in step b, the temperature of the heating reaction is reflux temperature, and the reaction time is 12h-13h.

[0035] The preferred raw material ratio and the amount of organic solvent added are conducive to the nucleophilic addition reaction of the aminosilane coupling agent and cerium acetylacetonate and grafting onto the surface of NiFe2O4@SiO2 core-shell nanoparticles.

[0036] Preferably, in step c, the mass ratio of the Ce-loaded NiFe2O4@SiO2 core-shell nanoparticles to the transition metal Lewis acid is 1:0.6-1:1.

[0037] Preferably, in step c, the second organic solvent is anhydrous ethanol or methanol.

[0038] Preferably, in step c, the mass-to-volume ratio of the Ce-loaded NiFe2O4@SiO2 core-shell nanoparticles to the second organic solvent is 1:20-1:30, wherein the unit of mass is gram and the unit of volume is milliliter.

[0039] Preferably, in step c, the temperature of the heating reaction is 80° C.-90° C., and the reaction time is 20 h-22 h.

[0040] The preferred raw material ratio and the amount of organic solvent added can promote the coordination between the transition metal and the N and O in the imine bond to form a stable six-membered ring structure.

[0041] Preferably, the preparation method of NiFe2O4@SiO2 core-shell nanoparticles specifically comprises the following steps:

[0042] Dissolve soluble nickel salt, soluble iron salt and citrate in deionized water, adjust the pH to 11-12, heat to 78-80°C, keep the temperature for 2h-3h, dry, and calcine to obtain NiFe2O4 nanoparticles;

[0043] The NiFe2O4 nanoparticles are dispersed in an ethanol aqueous solution, concentrated ammonia water and ethyl orthosilicate are added in sequence, and the mixture is stirred at 10°C-30°C for 20h-24h. The product is separated, washed, and dried to obtain the NiFe2O4@SiO2 core-shell nanoparticles.

[0044] The present invention prepares NiFe2O4 nanoparticles with excellent magnetic response performance through sol-gel, coats the surface of NiFe2O4 nanoparticles with silicon dioxide, reduces the agglomeration between NiFe2O4 nanoparticles, improves the dispersibility of NiFe2O4 nanoparticles, expands its specific surface area, and increases the loading sites.

[0045] Furthermore, the soluble nickel salt is nickel chloride, the soluble iron salt is ferric chloride, and the citrate is sodium citrate.

[0046] Furthermore, the molar ratio of the soluble nickel salt to the soluble iron salt is 1:2-1:2.2.

[0047] Furthermore, the molar ratio of the citrate to the soluble nickel salt is 1:5-1.5:5.

[0048] Furthermore, the molar volume ratio of the soluble nickel salt to deionized water is (1-2) mmol: (5-10) mL.

[0049] Further, sodium hydroxide is used to adjust the pH to 11-12.

[0050] If the alkalinity is too low, the magnetic properties of the prepared NiFe2O4 nanoparticles are poor, which is not conducive to the recycling of the catalyst; if the alkalinity is too high, the magnetic properties of the NiFe2O4 nanoparticles are not significantly improved, resulting in waste of raw materials and environmental pollution.

[0051] Furthermore, the calcination temperature is 500°C-700°C, and the calcination time is 4h-6h.

[0052] The preferred calcination temperature can ensure that the prepared NiFe2O4 nanoparticles have good saturation magnetization and meet the requirements of magnetic separation and recovery; at the same time, it can also make the prepared NiFe2O4 nanoparticles have a suitable particle size, thereby having a higher specific surface area, improving the loading capacity of the catalyst carrier, and also helping to improve the dispersibility of the catalyst in the reaction system, so that the catalyst can be more fully in contact with the reactants and improve the catalytic ability.

[0053] Furthermore, the mass ratio of water to anhydrous ethanol in the ethanol aqueous solution is 1:3-1:4.

[0054] Furthermore, the mass-to-volume ratio of the NiFe2O4 nanoparticles to the ethanol aqueous solution is 1-2:40-80, wherein the unit of mass is gram and the unit of volume is milliliter.

[0055] Furthermore, the mass-to-volume ratio of the NiFe2O4 nanoparticles to the concentrated ammonia solution is 1-2:1-2, wherein the unit of mass is gram and the unit of volume is milliliter.

[0056] The concentrated ammonia water mentioned in the present invention refers to industrial ammonia water with a concentration of 25wt%-28wt%.

[0057] Furthermore, the mass-to-volume ratio of the NiFe2O4 nanoparticles to tetraethyl orthosilicate is 1-2:0.8-1.5, wherein the unit of mass is gram and the unit of volume is milliliter.

[0058] The method for separating the products in the above-mentioned preparation process is all to use magnetic adsorption separation method.

[0059] The third aspect of the present application also provides the use of any of the above-mentioned magnetic nano bimetallic catalysts in the synthesis of 1,5-benzoxazepine compounds.

[0060] Further, using o-aminophenol represented by formula (II), diketone compound represented by formula (III) and aromatic aldehyde compound represented by formula (IV) as raw materials, and using any one of the above-mentioned magnetic nano bimetallic catalysts as a catalyst, a reaction is performed to obtain 1,5-benzoxazepine compound represented by formula (V);

[0061]

[0062] R1=H, CH3, Cl, Br; n=1, 2;

[0063] When X=C, R2 and R3 are CH3 or H;

[0064] When X=N, R2 and R3 are H.

[0065] The magnetic nano bimetallic catalyst provided by the present invention can be applied to the following reactions for preparing 1,5-benzazepine compounds:

[0066]

[0067] In the reaction of synthesizing the above-mentioned six-membered ring-fused 1,5-benzoxazepine compounds, the hydroxyl groups in the unsubstituted and substituted o-aminophenols as reaction substrates are not as reactive as the amino groups, which makes the reaction difficult to carry out. Strong alkaline catalysts are often used in the traditional catalytic synthesis of 1,5-benzoxazepine compounds. Such catalysts have limited selectivity, are prone to produce by-products, and the yield of the target compound is difficult to increase. They also cause environmental pollution, and the synthesis process is not green and economical.

[0068] The magnetic nano bimetallic catalyst provided by the present invention can not only be used as Lewis acid to activate the carbonyl group in the substrate of the nucleophilic substitution reaction, and activate the hydroxyl group in the unsubstituted and substituted o-aminophenol, but also can promote the intramolecular CC coupling cyclization of the intermediate, and can catalyze the synthesis of the target 1,5-benzoazaoxepine compounds in a green and efficient manner, with good selectivity and high catalytic activity. The catalyst can be stably separated and recovered from the reaction system, and the catalytic activity is not significantly reduced after multiple cycles of use, and has extremely high practical value for constructing an efficient and environmentally friendly catalytic synthesis system for 1,5-benzoazaoxepine compounds.

[0069] Specifically, when the bimetallic catalyst provided by the present invention is used to prepare the 1,5-benzoxazepine compound represented by formula (V), the steps include:

[0070] The substituted o-aminophenol represented by formula (II), the diketone compound represented by formula (III) and the bimetallic catalyst prepared above are added to an organic solvent, and the reaction is monitored by TLC until the reaction is completed. The aromatic aldehyde compound represented by formula (IV) is added to the reaction solution, and the reaction is monitored by TLC until the reaction is completed. The reaction is purified by recrystallization to obtain a 1,5-benzoxazepine compound represented by formula (V).

[0071] Exemplarily, the reaction temperature of the above-mentioned synthesis of 1,5-benzoxazepine compounds is 10°C-30°C.

[0072] Exemplarily, the organic solvent is 1,2-dichloroethane.

[0073] The magnetic nano bimetallic catalyst provided by the present invention can catalyze the organic reaction of different types of 1,5-benzoxazepine compounds, and has high catalytic activity and selectivity, and is easy to separate from the reaction system. At the same time, the catalyst has good stability and can be reused, and has potential practical value for constructing an efficient and environmentally friendly catalytic synthesis system for 1,5-benzoxazepine compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0074] Figure 1 Fourier transform infrared spectra (FT-IR) of the reaction products of each step prepared in Example 1 of the present invention, wherein, (a): NiFe2O4, (b): NiFe2O4@SiO2, (c): NiFe2O4@SiO2@PrNH2-Ce(acac)3, (d): NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2;

[0075] Figure 2 X-ray diffraction patterns (XRD) of the reaction products of each step prepared in Example 1 of the present invention, wherein: (a): NiFe2O4, (b): NiFe2O4@SiO2, (c): NiFe2O4@SiO2@PrNH2-Ce(acac)3, (d): NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2;

[0076] FIG3(a) is an X-ray photoelectron spectrum (XPS) of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 of the present invention;

[0077] FIG3(b) is the O1s electron binding energy spectrum of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 of the present invention;

[0078] Figure 3(c) is the C1s electron binding energy spectrum of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 of the present invention;

[0079] Figure 3(d) is the N1s electron binding energy spectrum of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 of the present invention;

[0080] FIG3(e) is the Ce 3d electron binding energy spectrum of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 of the present invention;

[0081] Figure 3(f) is the Cu 2p electron binding energy spectrum of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 of the present invention;

[0082] Figure 4 Scanning electron microscope images (SEM) of NiFe2O4 and NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 of the present invention, wherein (a): NiFe2O4, (b): NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2;

[0083] Figure 5 The particle size distribution diagram of NiFe2O4 nanoparticles and NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles prepared in Example 1 of the present invention;

[0084] Figure 6 Transmission electron microscopy (TEM) image of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 of the present invention;

[0085] Figure 7 N2 adsorption-desorption isotherms (BET) of NiFe2O4@SiO2 and NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 of the present invention;

[0086] Figure 8 This is the X-ray energy dispersion spectrum (EDS) of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 of the present invention;

[0087] Fig. 9 Thermogravimetric / differential thermal curve (TGA / DTA) of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 of the present invention;

[0088] Fig.10 Magnetic hysteresis loop diagrams (VSM) of NiFe2O4, NiFe2O4@SiO2 and NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 of the present invention, where (a): NiFe2O4, (b): NiFe2O4@SiO2, (c): NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2; the upper left corner is a diagram of the actual separation effect of the product with an external magnet. DETAILED DESCRIPTION

[0089] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0090] In order to better illustrate the present invention, further examples are given below.

[0091] All reagents in the following examples are commercially available unless otherwise specified, and all experimental methods are based on existing experimental methods unless otherwise specified.

[0092] The concentrated ammonia water used in the examples refers to industrial ammonia water with a mass concentration of 25%-28%. The room temperature in the following examples refers to 25℃-30℃.

[0093] Example 1

[0094] Preparation method of a magnetic nano bimetallic catalyst (NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2):

[0095] Step a, preparation of NiFe2O4 nanoparticles:

[0096] 2.38 g NiCl2·6H2O and 5.41 g FeCl3·6H2O (molar ratio 1:2) were weighed and added into a 250 mL three-necked flask, and then 0.5 g sodium citrate and 60 mL deionized water were added, and ultrasonic dissolution was performed. Under stirring conditions, the pH of the reaction solution was adjusted to 12 with 3 mol / L NaOH solution, and the temperature was raised to 80°C for 2 h. After the reaction mixture was cooled to room temperature, it was allowed to stand to obtain a brown-red sol. The sol was washed with anhydrous ethanol and deionized water for three times in sequence until the sol was neutral, and then dried in a vacuum drying oven at 100°C for 12 h to obtain a wet gel. The wet gel was calcined in a muffle furnace at 700°C for 6 h to obtain brown-red NiFe2O4 nanoparticles.

[0097] Step b, preparing NiFe2O4@SiO2 magnetic nanoparticles:

[0098] Weigh 2.0 g of the NiFe2O4 nanoparticles prepared above, add them to a mixed solution of 80 mL of anhydrous ethanol and 20 mL of deionized water, ultrasonically disperse them for 20 min, and then slowly add 2 mL of concentrated ammonia water under stirring conditions. After 30 min, add 1.5 mL of tetraethyl orthosilicate dropwise, stir and react at room temperature for 20 h, separate the product with an external magnet, wash it with anhydrous ethanol and deionized water for 3 times, and dry it in vacuo at 100 °C for 20 h to obtain NiFe2O4@SiO2 magnetic nanoparticles.

[0099] Step c, preparing NiFe2O4@SiO2 magnetic nanoparticles loaded with metal Ce(III):

[0100] Weigh 1.31 g of cerium acetylacetonate and add it to 27 mL of toluene, stir and dissolve for 20 minutes, then gradually add 0.66 g of (3-aminopropyl)triethoxysilane dropwise therein, stir and react at room temperature for 12 hours, then add 1.0 g of the NiFe2O4@SiO2 magnetic nanoparticles prepared above, reflux at 110°C for 12 hours, cool to room temperature, separate the product with an external magnet, wash it with anhydrous ethanol three times, and vacuum dry it at 100°C for 20 hours to obtain NiFe2O4@SiO2@PrNH2-Ce(acac)3.

[0101] Step d, preparation of NiFe2O4@SiO2 core-shell nanoparticles loaded with metal Ce(III) and Cu(II):

[0102] Weigh 0.8 g of the NiFe2O4@SiO2@PrNH2-Ce(acac)3 prepared above and 3 mmol Cu(OAc)2, add them into a 100 mL round-bottom flask, then add 24 mL of anhydrous ethanol, ultrasonically disperse, stir and react at 80 °C for 20 h, separate the product with an external magnet, wash it with anhydrous ethanol 3 times, 5 min each time, and vacuum dry it at 100 °C for 20 h to obtain the magnetic nano bimetallic catalyst NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2.

[0103] The specific reaction equation is as follows:

[0104]

[0105] Figure 1 The following are Fourier transform infrared spectra (FT-IR) of the reaction products prepared in each step of this embodiment. In the spectrum of NiFe2O4 magnetic nanoparticles (a), the stretching vibration peaks of the Fe-O bond and the Ni-O bond of NiFe2O4 appear at 606 cm -1 and 479cm -1 3455cm -1 and 1632cm -1 The broad peak at 1091 cm is the characteristic peak of the OH bond of water in the atmosphere. In the spectrum of NiFe2O4@SiO2 magnetic nanoparticles (b), it can be seen that at 1091 cm -1 and 803cm -1 The absorption peak of Si-O-Si bond appears, proving that SiO2 is successfully coated on the surface of NiFe2O4 magnetic core. In the spectrum of magnetic nanoparticles of NiFe2O4@SiO2@PrNH2-Ce(acac)3 (c), it can be seen that at 2935cm -1and 2854cm -1 The vibration peak is the result of the CH bond of the methylene group in the silane coupling agent, and the stretching vibration peak of the imine bond appears at 1661cm -1 The stretching vibration peak of the conjugated C=C bond appears at 1553 cm -1 665cm -1 The absorption peak at is the characteristic of the Ce-O bond in cerium acetylacetonate, and the above absorption peaks prove the immobilization of cerium acetylacetonate on NiFe2O4@SiO2@PrNH2. In the magnetic nanoparticle spectrum of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 (d), it can be seen that the imine bond absorption peak of curve (d) moves to a low frequency, proving that Cu is successfully coordinated with NiFe2O4@SiO2@PrNH2-Ce(acac)3, and copper acetate is loaded on the magnetic nanoparticles.

[0106] Figure 2 The X-ray diffraction patterns (XRD) of the reaction products prepared in each step of this embodiment. In (a), the 2θ values ​​of the diffraction peaks 18.38°, 30.14°, 35.63°, 37.26°, 43.18°, 53.75°, 57.29°, and 62.83° correspond to the (111), (220), (222), (311), (400), (422), (511), and (440) crystal planes of spinel nickel ferrite NiFe2O4 (JCPDS 10-0325), respectively, indicating the spinel structure of nickel ferrite. In (b)-(d), the diffraction peak type of each step product is similar to that of nickel ferrite, proving that the multi-step functionalization modification will not cause a significant change in the physical phase of NiFe2O4 magnetic nanoparticles. The particle sizes of the obtained NiFe2O4 and NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles were calculated by the Debye-Scherer equation and were 25.18nm and 29.15nm, respectively.

[0107] FIG3 is an X-ray photoelectron spectrum of the NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles prepared in this embodiment. The full spectrum of the NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles in FIG3(a) confirms the presence of eight elements: Ni, Fe, O, Si, C, N, Ce, and Cu. The characteristic peak of 530.3 eV appears in the spectrum of O1s in FIG3(b), which is attributed to the Ni-O bond and Fe-O bond in nickel ferrite, and the signal peak of Si-O bond at 532.8 eV proves the presence of NiFe2O4 magnetic nanoparticles coated with silica. The C-Si bond at 283.8 eV in FIG3(c) and the CN bond at 400.4 eV in FIG3(d) prove that a silane coupling agent has been introduced into the magnetic nanoparticles. The characteristic peaks of Ce-O bond at 529.3 eV and CO bond at 531.7 eV in Figure 3(b), the characteristic peaks of C=N bond at 288.1 eV and C=C bond at 285.6 eV in Figure 3(c) indicate the introduction of cerium acetylacetonate component. The binding energies of 904.6 eV and 899.6 eV in Figure 3(e) are Ce 3d 3 / 2 The characteristic peak of spin-orbit, Ce 3d 5 / 2 The characteristic peaks of Cu 2p are located at 886.8eV and 882.5eV, which is a favorable proof that the catalyst is successfully grafted with cerium acetylacetonate and the metal cerium is trivalent. 1 / 2 and Cu 2p 3 / 2 There are two characteristic peaks, the characteristic peaks at 962.1,eV and 953.7eV belong to Cu 2p 1 / 2 The characteristic peaks at 941.9 eV and 933.8 eV are consistent with the Cu 2p 3 / 2 This proves that Cu(Ⅱ) was successfully loaded on the surface of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2.

[0108] Figure 4 Scanning electron microscope (SEM) images of NiFe2O4 nanoparticles and NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles prepared in this example. Figure 4 As can be seen in (a), the nickel ferrite NiFe2O4 magnetic core is a spherical nanoparticle with agglomeration phenomenon. Figure 4 As can be seen in (b), after the NiFe2O4 magnetic core is coated with a silicon dioxide layer and grafted with cerium acetylacetonate and copper acetate, the particle size becomes larger, but its basic spherical morphology is not destroyed. Figure 4 (a) and Figure 4 (b) After particle size statistics, the particle size distribution is shown in Figure 5 As can be seen from the figure, the average particle size of NiFe2O4 nanoparticles is 26.0nm, and the average particle size of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles is 30.0nm, which further verifies the particle size calculation results of the XRD spectrum.

[0109] Figure 6 This is a transmission electron microscope (TEM) image of the NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles prepared in this embodiment. It can be seen from the figure that the inner layer of the catalyst prepared in this embodiment is a dark black magnetic core, and the outer layer is a light-colored fluffy substance with a core-shell structure. This is because the NiFe2O4 magnetic core is coated with silicon dioxide and modified with an organic chain; the nanoparticles of the catalyst are distributed more evenly, and the statistical data of the particle size distribution show that the NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles have a particle size of 30.3nm, which is relatively large, which is consistent with the analysis results of the SEM image.

[0110] Figure 7 The N2 low-temperature physical adsorption-desorption isotherms (BET) of the NiFe2O4@SiO2 nanoparticles and NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles prepared in this example. According to the IUPAC classification, the adsorption isotherms of NiFe2O4@SiO2 nanoparticles and NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles belong to type IV(a) with obvious H5 type hysteresis loops, indicating that the magnetic nanoparticles have mesoporous properties. The specific surface area of ​​NiFe2O4@SiO2 nanoparticles is 75.40cm 2 ·g -1 The specific surface area of ​​NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles is 53.30 cm 2 ·g -1 The pore volume of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles is 0.09cc·g -1 , the average pore size is 3.14nm.

[0111] Figure 8This is the X-ray energy dispersive spectrum (EDS) of the NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles prepared in this embodiment. It can be seen from the energy spectrum of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 that the prepared catalyst is mainly composed of eight elements, namely Ni, Fe, O, Si, C, N, Ce and Cu, which is consistent with the results of XPS characterization. The weight ratio and atomic ratio of Ni and Fe of about 1:2 indicate the presence of nickel ferrite NiFe2O4. The presence of N is attributed to the aminosilane coupling agent. The elemental content of Ce and Cu strongly proves the successful grafting of cerium acetylacetonate and the smooth coordination of Cu(III) ions. In addition, the precise content of Ce and Cu was analyzed by inductively coupled plasma atomic emission spectroscopy, and the Ce content was measured to be 4.98wt% and the Cu content was 10.03wt%.

[0112] Fig. 9 The thermogravimetric and differential thermal curves (TGA / DTA) of the NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nanoparticles prepared in this embodiment. The temperature was raised at a rate of 10°C / min in a N2 atmosphere, and the weight change of the catalyst was detected in the range of 25°C-800°C. In the first weight loss stage, the mass loss of 3.15% was the loss of water molecules and organic solvents remaining on the surface of the catalyst. The second step of weight loss occurred in the range of 107°C-384°C, and the mass loss of 16.39% was attributed to the thermal decomposition of the organic part of cerium acetylacetonate. In the third stage, the catalyst lost 5.23% weight in the temperature range of 384°C-520°C, which was due to the decomposition of the carbon skeleton of (3-aminopropyl)triethoxysilane. It can be calculated that the content of organic components is approximately 21.62% of the mass of the catalyst, that is, 2.28mmol·g -1 .

[0113] Fig.10 The magnetic hysteresis curves (VSM) of the magnetic nanoparticles NiFe2O4, NiFe2O4@SiO2 and NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in this example are shown in Figure 1. The reversible quasi-S-type magnetization curves without hysteresis loops prove the superparamagnetism of the composite material. The saturation magnetization (Ms) of NiFe2O4, NiFe2O4@SiO2 and NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 are 51.3emu·g -1 、44.5emu·g -1 and 36.8emu·g -1 The saturation magnetization intensity gradually decreases due to the grafting of non-magnetic functional groups on the surface of NiFe2O4 magnetic nanoparticles. Fig.10 As shown in the illustration, the NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 catalyst sample can still be easily separated from the solution. The prepared magnetic nanobimetallic catalyst has good saturation magnetization and coercive force and is easy to recycle and reuse.

[0114] Example 2

[0115] This embodiment provides a method for preparing a magnetic nano bimetallic catalyst (NiFe2O4@SiO2@PrNH2-Ce(acac)3-CuCl2), wherein steps a to c are exactly the same as those in Example 1, and step d is specifically as follows:

[0116] Weigh 0.8 g of the NiFe2O4@SiO2@PrNH2-Ce(acac)3 prepared above and 3 mmol CuCl2, add them into a 100 mL round-bottom flask, then add 30 mL of anhydrous ethanol, ultrasonically disperse, stir and react at 80 °C for 20 h, separate the product with an external magnet, and wash it with anhydrous ethanol 3 times, 5 min each time, and vacuum dry it at 100 °C for 20 h to obtain the magnetic nano bimetallic catalyst NiFe2O4@SiO2@PrNH2-Ce(acac)3-CuCl2.

[0117] Example 3

[0118] This embodiment provides a method for preparing a magnetic nano bimetallic catalyst (NiFe2O4@SiO2@PrNH2-Ce(acac)3-Pd(OAc)2), wherein steps a to c are exactly the same as those in Example 1, and step d is specifically as follows:

[0119] Weigh 0.8 g of the NiFe2O4@SiO2@PrNH2-Ce(acac)3 prepared above and 3 mmol Pd(OAc)2, add them into a 100 mL round-bottom flask, then add 30 mL of anhydrous ethanol, ultrasonically disperse, stir and react at 80°C for 20 h, separate the product with an external magnet, and wash it with anhydrous ethanol 3 times, 5 min each time, and vacuum dry it at 100°C for 20 h to obtain the magnetic nano bimetallic catalyst NiFe2O4@SiO2@PrNH2-Ce(acac)3-Pd(OAc)2.

[0120] Example 4

[0121] This embodiment provides a method for preparing a magnetic nano bimetallic catalyst (NiFe2O4@SiO2@PrNH2-Ce(acac)3-PdCl2), wherein steps a to c are exactly the same as those in Example 1, and step d is specifically as follows:

[0122] Weigh 0.8g of the prepared NiFe2O4@SiO2@PrNH2-Ce(acac)3 and 3mmol PdCl2, add them into a 100mL round-bottom flask, then add 30mL of anhydrous ethanol, disperse by ultrasonication, stir and react at 80℃ for 20h, separate the product with an external magnet, wash it with anhydrous ethanol 3 times, 5min each time, and vacuum dry it at 100℃ for 20h to obtain the magnetic nano bimetallic catalyst NiFe2O4@SiO2@PrNH2-Ce(acac)3-PdCl2. .

[0123] Catalytic activity evaluation:

[0124] 1. The bimetallic catalyst prepared in Examples 1-4 can be used as a catalyst for the preparation of the following six-membered ring-fused 1,5-benzoxazepine compounds:

[0125]

[0126] R1=H, CH3, Cl, Br; n=1, 2;

[0127] When X=C, R2 and R3 are CH3 or H;

[0128] When X=N, R2 and R3 are H.

[0129] 1.1 1,5-Benzoxizepine fused with 2-benzyl-cyclohexanone ring The catalytic activity of the prepared bimetallic catalyst was evaluated.

[0130] Take 6 clean 50mL dry flasks, add 1.0mmol o-aminophenol, 1.0mmol cyclic diketone and 10mg NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 in sequence, then add 3mL different organic solvents (toluene, acetonitrile, 1,2-dichloroethane), react at room temperature and reflux conditions respectively, TLC detection (developing solvent is dichloromethane and methanol in a volume ratio of 20:1) After the reaction is completed, without separating the intermediate, add 1.0mmol phenylacetaldehyde to the reaction solution, TLC detection (developing solvent is dichloromethane and methanol in a volume ratio of 20:1) After the reaction is completed, separate and recover the catalyst through an external magnet, filter, wash and dry to obtain a crude product. Add anhydrous ethanol dropwise to the obtained crude product at 78℃-80℃ until the crude product is completely dissolved, filter while hot, cool the filtered solution to precipitate crystals, filter, wash and dry to obtain the target product. The results showed that the best reaction conditions were 1,2-dichloroethane as solvent and room temperature.

[0131] Then, 1.0 mmol o-aminophenol, 1.0 mmol cyclic diketone, 3 mL 1,2-dichloroethane and different masses (0 mg, 5 mg, 15 mg, 20 mg, 25 mg, 30 mg) of NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 prepared in Example 1 were added to 6 50 mL dry flasks in turn, and the reaction was carried out at room temperature. After the reaction was completed by TLC detection, 1.0 mmol phenylacetaldehyde was added to the reaction solution without separating the intermediate, and the reaction was carried out at room temperature. After the reaction was completed by TLC detection, the catalyst was separated and recovered by an external magnet, and then filtered, washed and dried to obtain a crude product. Anhydrous ethanol was added dropwise to the obtained crude product at 78°C-80°C until the crude product was completely dissolved, and filtered while hot. After the filtered solution was cooled to precipitate crystals, it was filtered, washed and dried to obtain the target product. The specific reaction equation is as follows:

[0132]

[0133] The results of catalyst activity evaluation are shown in Table 1.

[0134] Table 1

[0135]

[0136]

[0137] Note: The reaction time in the table refers to the total reaction time; rt refers to room temperature, and reflux refers to reflux temperature.

[0138] The results show that the magnetic nano bimetallic catalyst (NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2) prepared in Example 1 exhibits excellent catalytic performance in catalyzing the domino three-component reaction to synthesize six-membered ring-fused 1,5-benzoxazepine compounds. When the optimal catalyst dosage is 20 mg, the reaction can be completed in 4.5 hours and can be carried out at room temperature. The yield of the target product can reach 84%, and the purity of the prepared product can reach 96%.

[0139] The catalyst recovered from the above reaction system is used again to catalyze the synthesis of 2-benzyl-cyclohexanone ring-fused 1,5-benzoxazepine according to the above method. The reaction of the compound, the catalyst dosage is 20 mg, the reaction time is 4.5 h, the reaction temperature is room temperature, after each reaction, a magnet is added to separate the catalyst, and it is washed with anhydrous ethanol 3 times as the catalyst for the next catalytic reaction. It was reused 6 times, and the catalytic activity did not decrease significantly, and the yield of the 6th cycle was 82.5%. It is proved that the magnetic nano bimetallic catalyst prepared in this example has good magnetic recyclability, excellent catalytic activity and stable cyclic catalytic ability, and is suitable for the synthesis of six-membered ring fused 1,5-benzoxazepine The compound provides a highly efficient and environmentally friendly catalyst.

[0140] The reaction temperature, reaction time, amount of raw materials and reaction solvent in steps a to d in Example 1 of the present invention are replaced by other conditions specified in the present invention. When the catalyst prepared is used to prepare the above-mentioned 1,5-benzoxazepine compounds, the technical effect equivalent to that of Example 1 can be achieved.

[0141] The catalytic activity of the magnetic nano bimetallic catalyst prepared in Example 2-4 was evaluated in the same manner as above, with the amount of catalyst used being 20 mg, the reaction time being 4.5 h, the reaction temperature being room temperature, and the other reaction conditions being identical. The results are shown in Table 2.

[0142] Table 2

[0143] Example 2 Example 3 Example 4 Yield (%) 75 80 78

[0144] The 2-benzyl-cyclohexanone ring-fused 1,5-benzoxazepine prepared using the bimetallic catalyst prepared in Example 2-4 as a catalyst The purity of the compound can reach 93%-95%. After being recycled for 6 times, the yield can still reach 72%-78%.

[0145] The NiFe2O4@SiO2@PrNH2-Ce(acac)3-Cu(OAc)2 nano bimetallic catalyst prepared in Example 1 of the present invention can be used to catalyze the synthesis of other 1,5-benzoxazepine compounds defined above, and the yield of the final product can reach 84%-92% and the purity can reach 95%-98%.

[0146] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modification, equivalent substitution or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A magnetic nano bimetallic catalyst, characterized in that: It includes a NiFe2O4@SiO2 core-shell nanoparticle carrier, and a cerium-based imine ligand and a transition metal Lewis acid chemically bonded and loaded on the carrier; Wherein, the structure of the cerium-based imine ligand is shown in formula (X): （Ⅹ） Wherein, m=3, 4; R is methyl or ethyl; The alkoxy group in the cerium-based imine ligand condenses with the hydroxyl group on the surface of the carrier to form a silicon-oxygen bond; and the N of the imine bond in the cerium-based imine ligand and the O connected to Ce are respectively coordinated with the metal atom in the transition metal Lewis acid to form a six-membered ring; the transition metal Lewis acid is copper chloride, copper acetate, palladium chloride or palladium acetate.

2. The magnetic nano bimetallic catalyst according to claim 1, characterized in that: The transition metal Lewis acid is copper acetate.

3. The magnetic nano bimetallic catalyst according to claim 1, characterized in that: The structure of the magnetic nano bimetallic catalyst is shown in formula (I): (Ι) Wherein, m=3, 4; R is methyl or ethyl; M is CuCl2, Cu(OAc)2, PdCl2 or Pd(OAc)2.

4. The method for preparing the magnetic nano bimetallic catalyst according to any one of claims 1 to 3, characterized in that: The steps include: Step a, preparing NiFe2O4@SiO2 core-shell nanoparticles; Step b, adding cerium acetylacetonate to a first organic solvent, adding an aminosilane coupling agent, mixing evenly, reacting, then adding the NiFe2O4@SiO2 core-shell nanoparticles thereto, heating the reaction, separating the product, washing, and drying to obtain NiFe2O4@SiO2 core-shell nanoparticles loaded with Ce; Step c, dispersing the Ce-loaded NiFe2O4@SiO2 core-shell nanoparticles and the transition metal Lewis acid in a second organic solvent, heating for reaction, separating the product, washing, and drying to obtain the magnetic nano bimetallic catalyst.

5. The method for preparing the magnetic nano bimetallic catalyst according to claim 4, characterized in that: In step b, the mass ratio of the NiFe2O4@SiO2 core-shell nanoparticles to cerium acetylacetonate is 1:1.2-1:1.5; and / or In step b, the mass ratio of the NiFe2O4@SiO2 core-shell nanoparticles to the aminosilane coupling agent is 1:0.6-1:1; and / or In step c, the mass ratio of the Ce-loaded NiFe2O4@SiO2 core-shell nanoparticles to the transition metal Lewis acid is 1:0.6-1:

1.

6. The method for preparing the magnetic nano bimetallic catalyst according to claim 4 or 5, characterized in that: In step b, the first organic solvent is toluene or n-hexane; and / or In step b, the aminosilane coupling agent is 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane or 4-aminobutyltriethoxysilane; and / or In step c, the second organic solvent is anhydrous ethanol or methanol.

7. The method for preparing the magnetic nano bimetallic catalyst according to claim 4, characterized in that: The preparation method of the NiFe2O4@SiO2 core-shell nanoparticles specifically comprises the following steps: Dissolve soluble nickel salt, soluble iron salt and citrate in deionized water, adjust the pH to 11-12, heat to 78-80°C, keep the temperature for 2h-3h, dry, and calcine to obtain NiFe2O4 nanoparticles; The NiFe2O4 nanoparticles are dispersed in an ethanol aqueous solution, concentrated ammonia water and ethyl orthosilicate are added in sequence, and the mixture is stirred at 10°C-30°C for 20h-24h. The product is separated, washed, and dried to obtain the NiFe2O4@SiO2 core-shell nanoparticles.

8. Use of the magnetic nano bimetallic catalyst according to any one of claims 1 to 3 in the synthesis of 1,5-benzoxazepine compounds, characterized in that: Using o-aminophenol represented by formula (II), a diketone compound represented by formula (III) and an aromatic aldehyde compound represented by formula (IV) as raw materials, and using the magnetic nano bimetallic catalyst described in any one of claims 1 to 4 as a catalyst, the reaction is carried out to obtain a 1,5-benzoxazepine compound represented by formula (V); R1=H, CH3, Cl, Br; n=1, 2; When X=C, R2 and R3 are CH3 or H; When X=N, R2 and R3 are H.

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